A simple transfer function for nonlinear dendritic integration

Relatively recent advances in patch clamp recordings and iontophoresis have enabled unprecedented study of neuronal post-synaptic integration (dendritic integration). Findings support a separate layer of integration in the dendritic branches before potentials reach the cell’s soma. While integration between branches obeys previous linear assumptions, proximal inputs within a branch produce threshold nonlinearity, which some authors have likened to the sigmoid function. Here we show the implausibility of a sigmoidal relation and present a more realistic transfer function in both an elegant artificial form and a biophysically derived form that further considers input locations along the dendritic arbor. As the distance between input locations determines their ability to produce nonlinear interactions, models incorporating dendritic topology are essential to understanding the computational power afforded by these early stages of integration. We use the biophysical transfer function to emulate empirical data using biophysical parameters and describe the conditions under which the artificial and biophysically derived forms are equivalent

Perceived Stress Predicts Altered Reward and Loss Feedback Processing in Medial Prefrontal Cortex

Stress is a significant risk factor for the development of psychopathology, particularly symptoms related to reward processing. Importantly, individuals display marked variation in how they perceive and cope with stressful events, and such differences are strongly linked to risk for developing psychiatric symptoms following stress exposure. However, many questions remain regarding the neural architecture that underlies inter-subject variability in perceptions of stressors. Using functional magnetic resonance imaging (fMRI) during a Monetary Incentive Delay (MID) paradigm, we examined the effects of self-reported perceived stress levels on neural activity during reward anticipation and feedback in a sample of healthy individuals. We found that subjects reporting more uncontrollable and overwhelming stressors displayed blunted neural responses in medial prefrontal cortex (mPFC) following feedback related to monetary gains as well monetary losses. This is consistent with preclinical models that implicate the mPFC as a key site of vulnerability to the noxious effects of uncontrollable stressors. Our data help translate these findings to humans, and elucidate some of the neural mechanisms that may underlie stress-linked risk for developing reward-related psychiatric symptoms.Psycholog

The Balloon Analog Insurance Task (BAIT): A Behavioral Measure of Protective Risk Management

Prior methods used to assess individual differences related to risk have not focused on an important component of risk management: how willing individuals are to pay for or take actions to insure what they already have. It is not clear whether this type of protective risk management taps into the same individual differences as does risk taking propensity measured by existing risk taking tasks. We developed a novel task to assess protective risk management, the Balloon Analog Insurance Task (BAIT), which is modeled after the Balloon Analog Risk Task (BART). In the BAIT, individuals are forced to decide how much money they are willing to pay in order to insure a specific fraction of their prior winnings given changing but imprecise levels of risk of monetary loss. Participants completed the BART and BAIT for real monetary rewards, and completed six self report questionnaires. The amount of insurance purchased on the BAIT was positively correlated with scores on the Intolerance of Uncertainty Scale and on the Checking scale of the revised Obsessive Compulsive Inventory. Conversely, the amount of insurance purchased was negatively correlated with scores on the Domain Specific Risk Taking Questionnaire, and on the Psychopathic Personality Inventory (PPI). Furthermore, relationships between insurance purchased and these scales remained significant after controlling for the BART in linear regression analyses, and the BART was only a significant predictor for measures on one scale - the PPI. Our results reveal that behavior on the BAIT taps into a number of individual differences that are not related to behavior on another measure of risk taking. We propose that the BAIT may provide a useful complement to the BART in the assessment of risk management style

Individual Differences in Dopamine Are Associated with Reward Discounting in Clinical Groups But Not in Healthy Adults.

Some people are more willing to make immediate, risky, or costly reward-focused choices than others, which has been hypothesized to be associated with individual differences in dopamine (DA) function. In two studies using PET imaging, one empirical (Study 1: N = 144 males and females across 3 samples) and one meta-analytic (Study 2: N = 307 across 12 samples), we sought to characterize associations between individual differences in DA and time, probability, and physical effort discounting in human adults. Study 1 demonstrated that individual differences in DA D2-like receptors were not associated with time or probability discounting of monetary rewards in healthy humans, and associations with physical effort discounting were inconsistent across adults of different ages. Meta-analytic results for temporal discounting corroborated our empirical finding for minimal effect of DA measures on discounting in healthy individuals but suggested that associations between individual differences in DA and reward discounting depend on clinical features. Addictions were characterized by negative correlations between DA and discounting, but other clinical conditions, such as Parkinson's disease, obesity, and attention-deficit/hyperactivity disorder, were characterized by positive correlations between DA and discounting. Together, the results suggest that trait differences in discounting in healthy adults do not appear to be strongly associated with individual differences in D2-like receptors. The difference in meta-analytic correlation effects between healthy controls and individuals with psychopathology suggests that individual difference findings related to DA and reward discounting in clinical samples may not be reliably generalized to healthy controls, and vice versa.SIGNIFICANCE STATEMENT Decisions to forgo large rewards for smaller ones due to increasing time delays, uncertainty, or physical effort have been linked to differences in dopamine (DA) function, which is disrupted in some forms of psychopathology. It remains unclear whether alterations in DA function associated with psychopathology also extend to explaining associations between DA function and decision making in healthy individuals. We show that individual differences in DA D2 receptor availability are not consistently related to monetary discounting of time, probability, or physical effort in healthy individuals across a broad age range. By contrast, we suggest that psychopathology accounts for observed inconsistencies in the relationship between measures of DA function and reward discounting behavior

From Blame to Punishment: Disrupting Prefrontal Cortex Activity Reveals Norm Enforcement Mechanisms

The social welfare provided by cooperation depends on the enforcement of social norms. Determining blameworthiness and assigning a deserved punishment are two cognitive cornerstones of norm enforcement. Although prior work has implicated the dorsolateral prefrontal cortex (DLPFC) in norm-based judgments, the relative contribution of this region to blameworthiness and punishment decisions remains poorly understood. Here, we used repetitive transcranial magnetic stimulation (rTMS) and fMRI to determine the specific role of DLPFC function in norm-enforcement behavior. DLPFC rTMS reduced punishment for wrongful acts without affecting blameworthiness ratings, and fMRI revealed punishment-selective DLPFC recruitment, suggesting that these two facets of norm-based decision making are neurobiologically dissociable. Finally, we show that DLPFC rTMS affects punishment decision making by altering the integration of information about culpability and harm. Together, these findings reveal a selective, causal role for DLPFC in norm enforcement: representational integration of the distinct information streams used to make punishment decisions

Variables influencing the neural correlates of perceived risk of physical harm

Abstract Many human activities involve a risk of physical harm. However, not much is known about the specific brain regions involved in decision making regarding these risks. To explore the neural correlates of risk perception for physical harms, 19 participants took part in an event-related fMRI study while rating risky activities. The scenarios varied in level of potential harm (e.g., paralysis vs. stubbed toe), likelihood of injury (e.g., 1 chance in 100 vs. 1 chance in 1,000), and format (frequency vs. probability). Networks of brain regions were responsive to different aspects of risk information. Cortical language-processing areas, the middle temporal gyrus, and a region around the bed nucleus of stria terminalis responded more strongly to high-harm conditions. Prefrontal areas, along with subcortical ventral striatum, responded preferentially to highlikelihood conditions. Participants rated identical risks to be greater when information was presented in frequency format rather than probability format. These findings indicate that risk assessments for physical harm engage a broad network of brain regions that are sensitive to the severity of harm, the likelihood of risk, and the framing of risk information

Using confirmatory factor analysis to measure contemporaneous activation of defined neuronal networks in functional magnetic resonance imaging

a b s t r a c t a r t i c l e i n f o Functional neuroimaging often generates large amounts of data on regions of interest. Such data can be addressed effectively with a widely-used statistical technique based on measurement theory that has not yet been applied to neuroimaging. Confirmatory factor analysis is a convenient hypothesis-driven modeling environment that can be used to conduct formal statistical tests comparing alternative hypotheses regarding the elements of putative neuronal networks. In such models, measures of each activated region of interest are treated as indicators of an underlying latent construct that represents the contemporaneous activation of the elements in the network. As such, confirmatory factor analysis focuses analyses on the activation of hypothesized networks as a whole, improves statistical power by modeling measurement error, and provides a theory-based approach to data reduction with a robust statistical basis. This approach is illustrated using data on seven regions of interest in a hypothesized mesocorticostriatal reward system in a sample of 262 adult volunteers assessed during a card-guessing reward task. A latent construct reflecting contemporaneous activation of the reward system was found to be significantly associated with a latent construct measuring impulsivity, particularly in males

Behavioral/Systems/Cognitive Midbrain Dopamine Receptor Availability Is Inversely Associated with Novelty-Seeking Traits in Humans

Novelty-seeking personality traits are a major risk factor for the development of drug abuse and other unsafe behaviors. Rodent models of temperament indicate that high novelty responding is associated with decreased inhibitory autoreceptor control of midbrain dopamine neurons. It has been speculated that individual differences in dopamine functioning also underlie the personality trait of novelty seeking in humans. However, differences in the dopamine system of rodents and humans, as well as the methods for assessing novelty responding/seeking across species leave unclear to what extent the animal models inform our understanding of human personality. In the present study we examined the correlation between novelty-seeking traits in humans an